Atherogenic metabolism leads to atherosclerosis and is characteristic of a cellular energy deficiency, by blocked oxidative phosphorylation, negative nitrogen balance and increased proteolysis. Atherogenic metabolism accompanies diabetes mellitus type I and II, essential hypertension (linked to diabetes), chronic sublethal cyanide poisoning, such as by heavy cigarette smoking, acute cyanide poisoning, from fire smoke inhalation, and syndrome X, which is an insulin resistant state that precedes the disorders of diabetes mellitus, hypertension, certain dislipidemias, and premature atherosclerotic vascular disease.
There are two important alternatives to glucose as a fuel: amino acids (from functional protein) and triglycerides (from the body's fat stores). In the disturbed metabolism of diabetes and cyanide toxicity, selective proteolysis of functional intracellular proteins occurs to provide the amino acid precursors for the Krebs cycle, in an attempt to restore energy production which has been incorrectly perceived by the body as starvation.
This proteolytic state is highly atherogenic due to excessive sulphur metabolism (with increased methionine, homocysteine, and cysteine metabolism), and the presence of oxidants and free radicals. It is also associated with the transportation of increased amounts of triglyceride from fat stores. It is precisely this atherogenic proteolytic state which is responsible for 75% of diabetic deaths. It also causes 80% of deaths in individuals with chronic sub-lethal cyanide toxicity and Syndrome-X.
This energy depleted atherogenic, proteolytic state causes activation of the important enzyme glutamine synthetase (GS). GS activity is associated with the disturbed metabolism of diabetes mellitus, heavy smoke inhalation, and essential hypertension where it is linked to non-insulin dependent diabetes mellitus and lipid disturbances such as Syndrome-X. These states share equal importance as major risk factors for atherosclerosis.
When the body is able to metabolize glucose (the diabetic metabolism is adequately corrected, cyanide levels are low and the body is not starved) GS will be substantially inactive. The atherogenic proteolytic state is not present. When the body is unable to metabolize the preferred fuel, glucose, the proteolytic metabolic shift will occur and this will necessitate activation of GS and degradation of thiocyanate.
It is known that normalizing glycemic levels will reduce atherosclerosis in diabetics. It is predicted that better control of the disordered, atherogenic diabetic metabolism earlier in the course of an illness will reduce diabetic deaths caused by atherosclerosis.
Reagents are known for screening and for monitoring such abnormal metabolic conditions. Most reagents focus directly upon the function of the pancreas by monitoring the levels of pancreatic products, such as insulin, within body fluids. Others measure the level of glucose within body fluids. However, these tests can be invasive and are often inadequate to determine atherogenesis. In particular, in these atherogenic disorders it is the energy deficiency of the cells which is of concern. The levels of, for example, glucose and insulin are not directly indicative of this cellular state since these levels can vary in relation to various effects, such as exercise, glucose consumption, insulin antibodies and insulin resistance.
The earliest methods for monitoring cellular energy deficiencies by abnormal glucose and/or lipid metabolism measured protein metabolism by means of a whole body nitrogen balance. However, many problems were associated with these methods as set out in Joslin's Diabetes Mellitus, 1994, p. 118.
A reagent is known as described in published Canadian patent application s.n. 2,072,423 which allows screening for atherogenic metabolic abnormal conditions by observing a color change when the reagent is introduced to saliva. However, this reagent has some disadvantages. For example, a specific ratio of saliva to reagent is required to obtain reproducible and accurate results and there has been difficulty in differentiating between color changes in some lighting conditions. In addition, it has been found that there is not a clear color distinction between a moderate risk condition and an actual pathology.
A test-strip is required which will enable early discovery of atherogenic metabolism. As well, a test is required which can be conducted by untrained, as well as trained, persons.